Biomedical Microdevices (2022) 24:32

https://doi.org/10.1007/s10544-022-00631-1

Biosensors for detection of prostate cancer: a review

Sourav Sarkar1 · Manashjit Gogoi1   · Mrityunjoy Mahato2 · Abhijeet Balwantrao Joshi3 · Arup Jyoti Baruah4 ·
Prashant Kodgire3 · Polina Boruah5

Accepted: 19 August 2022

© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022

Abstract
Diagnosis of prostate cancer (PC) has posed a challenge worldwide due to the sophisticated and costly diagnostics tools,
which include DRE, TRUS, GSU, PET/CT scan, MRI, and biopsy. These diagnostic techniques are very helpful in the detec-
tion of PCs; however, all the techniques have their serious limitations. Biosensors are easier to fabricate and do not require
any cutting-edge technology as required for other imaging techniques. In this regard, point-of-care (POC) biosensors are
important due to their portability, convenience, low cost, and fast procedure. This review explains the various existing diag-
nostic tools for the detection of PCs and the limitation of these methods. It also focuses on the recent studies on biosensors
technologies as an alternative to the conventional diagnostic techniques for the detection of PCs.

Keywords  Prostate cancer · Point of Care · Biosensor · Paper based · Microfluidic · Lateral flow assay

1 Introduction per 100,000 US people (Hariharan et al. 2016). The com-

Prostate cancer (PC) is a lethal disease and the second most
prevalent type of cancer among men. Siegel et al. reported
that 31620 patients died of PC in the USA during the year
2018 (Siegel et al. 2019). In general, the risk of PCs is quite
high i.e., 1 out of 8 men is diagnosed with PC in his life-
time (Key Statistics for Prostate Cancer, American Cancer
Society). In India, the number of PC cases is lower than
that of other western countries. The annual PC rate was
reported to be 5-9.1 cases per 100,000 people in a year and
it is 110.4 cases for white males and 180.9 for black males
* Manashjit Gogoi
manash.aec@gmail.com
1
Department of Biomedical Engineering, North-Eastern Hill
University, Shillong 793022, Meghalaya, India
2
Physics Division, Department of Basic Sciences and Social
Sciences, North-Eastern Hill University, Shillong 793022,
Meghalaya, India
3
Biosciences and Biomedical Engineering, Indian Institute
of Technology, Indore‑453552, Madhya Pradesh, India
4
Department of General Surgery, North Eastern Indira Gandhi
Regional Institute of Health and Medical Sciences, Shillong,
Meghalaya, India
5
Department of Biochemistry, North Eastern Indira Gandhi
Regional Institute of Health and Medical Sciences,
Shillong‑793018, Meghalaya, India
mon symptoms for PCs are repeated urination, urination
problem, worn-out urinary stream, blood in urine or semen,
and acute pain in the lower portion of the back, hips, or
thighs. However, prostatitis or benign prostatic hyperplasia
also might have similar symptoms. Therefore, it is very
difficult to detect PCs from conventional symptoms. It has
been reported that PC is diagnosed mostly in the population
above 50 years and rarely diagnosed below 50 years of age.
Genetic factors are one of the most common risk factors for
PC. The risk of transmission of PC to the next generations
of a patient is found to increase 2-4 folds.
The most common biomarker used for the identification
of PC is the prostate-specific antigen (PSA), a 33 kD pro-
enzyme that belongs to the kallikrein group of proteases
namely human kallikrein 3 (hK3). In seminal fluid, its con-
centration ranges from 0.5-2 g/L (Stenman et. al. 1999). PSA
is also found in the saliva (Khan et al. 2018) and urine of men
(Kearns and Lin 2018). The concentration of PSA is 0.03-
0.34 ng/mL (Ayatollahi et al. 2007) in saliva and men hav-
ing PSA 1.7 ng/mL in their saliva are evident of having PC
(Farahani et al. 2020). The amount of total PSA in healthy
individuals is 0-4 ng/mL, however it surges in case of PC
patients (Luderer et al. 1995). Human glandular kallikrein2
(hK2) and prostate cancer gene 3 (PCA3) are different bio-
markers used for the detection of PC and are found in human
serum (Mao et al. 2018). hK2 is a serine protease, and its

13
Vol.:(0123456789)
 32   Page 2 of 12
amino acid sequence is 79% homologous to that of PSA
(Klee et al. 1999). The normal concentration of hk2 should
be <0.05 ng/mL and >0.05 ng/mL for patients with PC
(Becker et  al. 2000). The PCA3 and sarcosine are two
other biomarkers of PC present in urine with a normal con-
centration range of 2-10 ng/mL (Ferro et al. 2016). PCA3
is a non-coding RNA and found only in human prostate
tissue (Gutschner and Diederichs 2012). Semen exosomes
contain miRNA which also acts as a biomarker for the
detection of PC (Barcelo et al. 2019).
Digital rectal examination (DRE), transrectal ultra-
sound (TRUS), gray-scale ultrasonography (GSU), posi-
tron emission tomography/computer tomography (PET/
CT) scan, power doppler ultrasonography (PDU), three-
dimensional contrast-enhanced power Doppler ultrasonog-
raphy (3D-CE-PDU), transrectal magnetic resonance
imaging (TMRI), PSA level test, and biopsy are the most
widely used conventional diagnostic techniques for the
examination of PC. All of these diagnostic techniques have
their advantages as well as disadvantages. For example,
simple and cost-effective techniques have poor sensitivity
whereas highly sensitive techniques are very expensive
and not easily available to the masses. Biosensors can be
used as low-cost alternative tools to the costly conven-
tional instruments for the detection of PCs. In this review,
we have discussed the conventional detection techniques
and various kinds of biosensors for the identification of
PCs along with their challenges and future prospects.
2 Conventional diagnostic techniques
for PC detection
DRE is a simple diagnostic procedure used to examine the
lower rectum and other internal organs. It is one of the easi-
est and quickest ways to check the health of a prostate gland
(Schroder et al. 1998). DRE has poor performance in lower
concentrations of PSA and hence, DRE alone is insufficient
for detecting PC.
In TRUS, ultrasound waves are allowed to interact with
the walls of the rectum and the neighboring areas of the
prostate. The waves rebound from the organs and tissues
are transformed into anatomical images and then displayed
on the computer screen. TRUS biopsies are taken randomly
without targeting any cancer lesions, therefore, are prone to
diagnostic errors. DRE technique is useful for patients hav-
ing PSA levels >4 ng/mL (Puech et al. 2013).
GSU is a traditional imaging method for PC and provides
greater temporal and spatial resolution compared to PDU.
GSU can detect microbubbles which are used as a contrast
agent for better imaging and ultrasonography (US). PDU
uses doppler imaging technique and allows sensitive detec-
tion of fluid flowing blood vessels present in the prostate.
13
Biomedical Microdevices (2022) 24:32
3D-CE-PDU is found to be more efficient and accurate
than PDU (Unal et al. 2000). The micro-vessels in malig-
nant tumors are smaller and uniform than benign or nor-
mal tissues. If the microvascular density increases in PC,
these imaging techniques fail to detect the malignant lesions
(Halpern 2006).
PET/CT scan is used generally to detect and locate
malignant PC. The malignant prostate tumors located at the
transition zone, are often missed by conventional imaging
techniques. PET/CT scan is not sufficient for differentiating
cancerous prostate lesions from benign hyperplasia, but it
can at least detect local recurrence and lymph node metas-
tasis (Schmid et al. 2005).
MRI produces comprehensive 3D images of soft tissues
or organs of the human body. MRI is found to be a superior
technique for cancer compared to other techniques. The
levels of PSA in the human body sometimes are elevated
due to other benign factors and result in wrong predic-
tions, which can be confirmed through the biopsy process.
In such cases, MRI is predictive enough to dismiss these
kinds of negative reports (Kirkham et al. 2006). However,
it is expensive and available in sophisticated laboratories.
PSA is a common biomarker used for detecting PC
using fluorescence techniques (Harma et al. 2001), and
enzyme-linked immunosorbent assay (ELISA) (Chang
et  al. 2018, Stowell et  al. 1991), and bioluminescent
enzyme immunoassay (Seto et al. 2001). PSA levels may
increase even in a variety of non-cancerous conditions,
like infection, trauma, inflammation in the prostate, as
well as in benign prostatic hyperplasia. Hence, PSA moni-
toring might have low accuracy (Yao et al. 2018).
The tissues in the prostate gland are tested for malig-
nancy during a prostate biopsy. In order to perform biopsy,
the prostate tissue section is collected using a needle. It is
usually recommended for PSA levels ranging from 4 - 10
ng/mL (Matlaga et al. 2003).
3 Biosensors for prostate cancer detection
As per the International Union of Pure and Applied Chem-
istry (IUPAC), the definition of "biosensor" is “a device that
uses specific biochemical reactions mediated by isolated
enzymes, immunosystems, tissues, organelles or whole cells
to detect chemical compounds usually by electrical, thermal
or optical signals” (Jurado-Sanchez 2018). These devices
detect signals as per the concentration of the analyte in bio-
logical samples and convert them to measurable signals with
the help of a transducer. A bioreceptor or biorecognition
element is connected with transducers to detect the pres-
ence and amount of the analyte. The analytes interact with
bioreceptors and the signals are recorded by the transducers,
which gives qualitative and quantitative values of the analyte
Biomedical Microdevices (2022) 24:32 Page 3 of 12  32
(Fig. 1). These devices are categorized as per the biorecog-
nition elements or transducers used. For detection of PCs,
biosensors are required because of the fact that the conven-
tional diagnostics techniques are either not efficient or very
expensive. Biosensors are cost-effective and portable.
The biosensors reviewed in this report, have been clas-
sified according to the types of transducers used, and the
applications of these biosensors for the identification of PC
are discussed in the following sections.
3.1 Electrochemical biosensors
Biochemical reactions such as reactions between enzymes-
substrates and antigen-antibody are converted to electrical
signals (e.g., current, voltage, impedance, etc.) by electro-
chemical biosensors. Clark was the first to conceptualize
an electrochemical biosensor in 1962, and he explained the
functioning of glucose enzyme electrodes for monitoring
blood glucose levels (Clark and Lyons 1962). The glu-
cose electrochemical biosensor was fabricated with three
screen-printed electrodes (SPE) viz. working electrode
(iridium-containing carbon), reference electrode (Ag/
AgCl), and counter electrode (Au). (Fig. 2i) (Shen et al.
2007). In another study, a biosensor was fabricated with
PLLA (carboxylated poly-L-lactide) nanoparticles along
with ssDNA conjugated GO (graphene oxide)-for detecting
Fig. 1  Schematic representation of a biosensor (Damborsky et  al.
2016), which uses various biological elements such as enzymes, anti-
bodies, proteins, etc. The analyte (sample) reacts with the biorecogni-
tion element which helps the biosensor to measure the amount of ana-
two biomarkers simultaneously i.e., VEGF and PSA using
two-electrode electrochemical technique (Fig. 2ii). It was
one of the earliest label-free electrochemical biosensors
for rapid and accurate detection of two cancer biomarkers
(Pan et al. 2017). Screen-printed electrodes (SPE) were
used for developing an immunochromatographic biosensor
(electrochemical) for the swift and accurate identification
of PSA. The biosensor had a test strip that consisted of
four specific zones viz. sample loading zone, conjugation
zone, test zone, and absorption zone (Fig. 2iii). The SPE
was placed underneath the test zone of the strip. Then the
secondary antibodies are bound to the specific analytes.
This binding resulted in the propagation of electrical sig-
nals which were detected by the SPE corresponding to the
analyte concentration (Lin et al. 2008).
A PC biosensor was fabricated using oligonucleo-
tide with MWCNT composite by detecting miRNA-141
using electrochemical technique. Peptide nucleic acids or
locked nucleic acids could be used to increase sensitivity
and LOD due to their higher attraction toward miRNA-
141 (Tran et al. 2013). A PSA sensor was fabricated by
electrochemical immunoassay using magnetic beads with
LOD < 0.1 ng/mL (Sarkar et al. 2008). Another total PSA
sensor was developed using horseradish peroxidase-labeled
antibody on the SPE electrode (Sarkar et al. 2002). A dual
mode (impedimetric and amperometric) PSA biosensor
lyte present in the substrate. It is converted to measurable signals by
the transducer. Reproduced with permission from Damborsky et  al.
(2016)
13
 32   Page 4 of 12
was developed using gold nanoparticle assembly with
LOD upto 10 ng/mL (Jolly et al. 2017). In another study,
a microfluidic PSA sensor was fabricated by coating GO-
Fe3O4 composite on SPE electrode with anti-PSA antibod-
ies and the LOD was found to be 15 fg/mL in serum sam-
ple (Sharafeldin et al. 2017). PSA detection was reported
using rolling circle amplification (RCA) reaction using
poly(thymine)-coated CuNP with LOD of 0.02 ± 0.001
fg/mL (Zhu et al. 2016).
3.2 Optical biosensors
An optical biosensor uses an optical transducing system,
which include surface plasmon resonance (SPR), local-
ized SPR, interferometers, optical resonators, gratings, and
refractometers. These biosensors send optical signals that
are correlated with the concentration of the analyte (Chen
and Wang 2020; Ramsden 1997). The surface of the trans-
ducer consists of biorecognition elements such as antibody
molecules or molecules with special affinity properties
(Homola et al. 1999).
Fluorescent immunoassay, radioimmunoassay, and ELISA
have been used as conventional techniques which are reported
to be specific and sensitive. But these methods need skilled
manpower, are expensive, and time-consuming. Optical bio-
sensors use quantum dots and luminescent nanoparticles,
Fig. 2  (i) Front view of a screen-printed electrode (Shen et al. 2007)
(ii) Schematic diagram of modified biosensor where the working and
counter electrodes are induced together and the reference electrode
remains separated (Pan et al. 2017) (iii) Schematic representation of
13
Biomedical Microdevices (2022) 24:32
which have better photostability and tunable emission prop-
erties (Sapsford et al. 2006). Surface plasmon resonance
(SPR) is a resonant vibration of the conduction electrons of
metal using a polarized light at a specific angle i.e., angle
of resonance (Amendola et al. 2017). Some optical biosen-
sors need an SPR chip that contains a functional layer of
interacting molecules. The working principle of SPR biosen-
sors and functionality have been reviewed (Hoa et al. 2007,
Homola 2008). The resonance in SPR is measured in terms
of wavelength, incidence angle and intensity of reflected light
(Fig. 3).
CdSe/ZnS QD based biochips were fabricated using
surface plasmon coupled emission (SPCE) technique. PSA
was immobilized on SPR glass substrate to fabricate the
protein chips. Initially, a gold coated glass was dipped in
piranha solution for a short time to eliminate impurities
and activate the substrate for PSA immobilization. The
substrate was then treated for 3 hours in 3-(aminopropyl)
trimethoxysilane solution (APTMS) to activate amine
functional groups and the PSA protein was immobilized
on it. Sensitivity of the biochips improved due to the pres-
ence of QDs and the LOD achieved was equal to 10 fg/mL
(Jin et al. 2012). A carbon substrate with QD streptavi-
din conjugate-based biosensor for PSA was reported with
LOD value of 0.25 ng/mL (Kerman et al. 2007). A SPR
biosensor was constructed using PSA-⍺1ACT monoclonal
the electrochemical biosensor. (A) test strip, (B) cover, (C) bottom
cover, and (D) screen-printed electrodes (Lin et al. 2008) Reproduced
with permission from Shen et al. (2007); Pan et. al. (2017), and Lin
et al. (2008)
Biomedical Microdevices (2022) 24:32 Page 5 of 12  32
antibody for detection of PC (Jang et al. 2009). A micro-
contact imprinting-based SPR biosensor was fabricated
for detecting PSA in clinical samples. It has several advan-
tages, like less activity loss in biorecognition molecules
and a very small sample requirement (Erturk et al. 2016).
Localized surface plasmon resonance (LSPR) is an
optical phenomenon that occurs while incident light inter-
acts with surface electrons in a conduction band (Willets
and Duyne 2007). The resonance frequency of LSPR is
dependent on the nanoparticles' characteristics such as
structural arrangement, size, charge, interplanar distance,
etc. (Petryayeva and Krull 2011). A ultrasensitive LSPR
fiber optic biosensor was designed using gold nanodisk
arrays for PSA detection with LOD of 0.1 pg/mL (Kim
et al. 2019). A LSPR biosensor was developed by modi-
fying the surface of silica nanoparticles with LOD of 10
ng/mL (Endo et al. 2005). Magnetic nanobeads coupled
with a peptide were used to create a biosensor based on
the SPR phenomenon with very low turnaround time and
LOD was 100 pg/mL (Esseghaier et al. 2014). Another
LSPR-based biosensor claimed to detect PSA even at 500
pg/mL in mixed human blood in a short time. It contained
32 sensor sites distributed across eight microfluidic chan-
nels (Acimovic et al. 2014). A QD-paper-based optical
biosensor was reported for simultaneous detection of CEA
(carcinoembryogenic antigen) and PSA with LOD of 0.3
ng/mL and 0.4 ng/mL, respectively (Chen et al. 2019). A
biosensor based on nanodisk-array was fabricated which
could detect PSA with a LOD of 100 fg/mL (Sanders et al.
2014).
Photonic crystal biosensors are widely used for PC detec-
tion, which can controls the propagation of electromagnetic
waves that interact with it. Biosensors with photonic crystal
structures are used to detect different types of analytes with
great efficiency and precision. A photonic crystal-based
biosensor was reported for detecting PSA concentrations as
lesser as 0.5 ng/mL. The device was fabricated using elec-
tron beam lithography technique (Sana et al. 2017). Another
Fig. 3  Representation of SPR
phenomenon (a) prism-coupled
arrangement, (b) resonance
deviation in the reflected light
prism. Reproduced with permis-
sion from Hoa et al. (2007)
very sensitive photonic crystal nanolaser biosensor was
investigated for detection of PSA by measuring the move-
ment of laser wavelength. The gadget was very thermosta-
ble and reported to be extremely sensitive to other proteins
(Hachuda et al. 2015).
3.3 Piezoelectric biosensors
The piezoelectric effect is the capacity of certain materials
to generate an electrical signal as a result of applied mechan-
ical stress. QCM (quartz crystal microbalance) is a piezo-
electric biosensors, which can detect PSA by the change in
resonance frequency as per the change of mass on the sensor
surface (Kwak and Lee 2019). Figure 4 shows a schematic
quartz crystal microbalance. The compression can be in the
form of external pressure.
Metallic electrodes were partially deposited on both
sides of a circular quartz crystal to make the QCM. Gold
electrodes are commonly used in biosensing applications.
The quartz crystal detector used in QCM resonates at the
fundamental frequency when an electric field is applied to
it (Skladal 2016; Su et al. 2013).
These biosensors work on different resonator modes such
as (i) thickness extensional (TE) mode, (ii) thickness-shear
(TS) mode, (iii) lateral extensional (LE) mode, and (iv) flex-
ural mode (flex). TE mode resonator provides highest sen-
sitivity as it can generate higher wave velocity and resonant
frequency than other existing resonators, and it is found to
be better in liquid medium (Pang et al. 2012).
PSA and alpha-fetoprotein (AFP) were detected using
a label-free, inexpensive and rapid piezoelectric biosensor
with sensitivity of 0.25 ng/mL and faster detection (within
30 minutes) (Su et al. 2017). A piezoelectric microcanti-
lever based PSA biosensor was fabricated by Gupta et al.
using COMSOL multiphysics modeling and using lead
zirconate titanate (PZT) and SiO2 with detection range
of 2 ng to 8 ng (Gupta and Swaminathan 2015). A PZT
13
 32   Page 6 of 12
microcantilever with immobilized PSA antibodies was
employed for PSA detection through antibody and antigen
binding (Lee et al. 2005). Gopinath et al. (2015) fabricated a
biosensor based on microcantilever for detection of various
diseases. Whenever the antigen/microorganisms come in
contact with the chemically sensitive material on its surface,
it results in bending of the microcantilever. These cantile-
vers have tremendous potential due to ease of combining
a PZT nanomechanical cantilever and immobilization of
proteins on them which help in making portable label-free
diagnostic devices.
4 Emerging biosensors
4.1 Microelectromechanical system (MEMS)‑based
biosensor
A MEMS-based biosensor is fabricated by depositing
an analyte sensitive layer on the top of a microcantile-
ver which ensures biological recognition. The detection
of the analyte by the bioreceptors of the sensitive layer
creates a difference of stress between the sensitive layer
and the microcantilever which results in deflection of the
microcantilever. A MEMS sensor using paper as a struc-
tural material was fabricated to be useful as paper-based
piezoresistive force sensor (Fig. 5). The conductive materi-
als patterned on the paper produced a piezoresistive effect
(Liu et al. 2011). MEMS microcantilever sensors are also
helpful in quick detection of various antigens present in the
body through binding with antibodies immobilized on the
cantilever surface and subsequent deflection of the canti-
levers (Vashist 2007). The detection of various diseases
like tuberculosis, HIV, etc., which can be made faster using
MEMS sensors. Feng et al. fabricated a giant magneto-
impedance (GMI) sensor using photolithography and wet
etching methods with LOD to be 0.1 ng/mL (Feng et al.
2019). MEMS sensors require lesser materials to fabricate
which makes them cheaper, easy to use and very much
favorable for POC diagnostics.
Fig. 4  Schematic representation
of Quartz crystal microbalance.
Reproduced with permission
from Marrazza (2014)
13
Biomedical Microdevices (2022) 24:32
4.2 Paper‑based biosensor
Paper-based biosensors are emerging biosensors based on
optical and electrochemical detection methods. The vari-
ous physical properties of paper such as density, resilience,
and weight can be tuned as per requirement. Paper consists
of cellulose fiber which is a hydrophilic fibre matrix that
helps in the easy transportation of liquid (Ratajczak and Sto-
beicka 2020). The properties of hydrophilic fiber can also
be adjusted to change its properties such as hydrophilicity,
permeability and reactivity. The use of paper-based devices
is user friendly, biodegradable, low cost, easily hydrophilic
and hydrophobic patterned etc. (Shergujri et al. 2019; Nery
and Kubota 2013). Paper-based biosensors are categorized
as dipstick assays, lateral flow assays (LFA), microfluidic
paper-based analytical devices (µPADs) etc.
Dipstick assays contain previously-stored reagents into a
blotting paper, which are submersed into the analyte solu-
tions and subsequently, the color is changes proportional to
the analyte concentration (Hu et al. 2014). Dipstick assay
is used for optical detection in qualitative manner, which
may not be suitable for diagnosis (Posthuma-Trumpie et al.
2009). Lateral flow assays (LFAs) have the reagents immo-
bilized on the strip and the sample is allowed to flow along
the longitudinal direction of the strip. ELISA methods are
used in LFAs, which comprises four specific sections such
as sample pad, conjugation pad, detection pad, and wicking
pad (Lee et al. 2013, Lin et al. 2015) which help in effi-
cient detection of analytes. Multiple (Hu et al. 2017) and
quantitative assays (Urusov et al. 2019) can be performed
using LFAs. Fu et al. (2019) investigated a surface-enhanced
Raman scattering (SERS) based LFA for quick detection of
PCA3 (prostate cancer antigen 3) mimic DNA with LOD
of 3 fM. An ICTS (immunochromatography test strip) plat-
form was fabricated using QD beads for quick detection of
PSA with LOD of lower than the accepted level for clinical
diagnosis (Li et al. 2014). A fluorescence ICTS was devel-
oped to detect PSA quickly by utilizing a novel amphiphi-
lic hydrophobin (HFBI) protein with sensitivity of 0.06 ng/
mL (Zhang et al. 2018). A highly sensitive LFA for detec-
tion of fPSA (free PSA) was developed using fluorescent
Biomedical Microdevices (2022) 24:32 Page 7 of 12  32
Fig. 5  Paper-based piezoresistive force sensors. (A) Diagrammatic
representation of the sensor. (B) The process of development of the
sensor. Reproduced with permission from Liu et al. (2011)
europium(III) chelate doped nanoparticles with a LOD of
0.01 ng/mL (Salminen et al. 2019). Semiconductor poly-
mer dots were used as a fluorescent probe in another ICTS
which could detect PSA, AFP (alpha fetoprotein) and CEA
(carcinoembryonic antigen) within 10 minutes with LODs
well below the accepted level for clinical detection (Fang
et al. 2018). In LFA, binding of analytes with their specific
biomarker produces results. LFAs are commonly used in
POC diagnosis due to its comprehensibility, affordability,
and capability to produce quick results.
The microf luidic paper-based analytical devices
(μPADs) are mostly used for POC diagnostics. Cellulose
is used as a substrate in μPADs, which helps the micro-
fluidic devices in performing flow of fluid without any
external source of energy. μPADs can be used for sim-
ple qualitative tests as well as more complex and diffi-
cult qualitative tests (Arugula and Simonian 2014). Some
special fabrication methods are employed to create hydro-
philic channels on hydrophobic paper (Rezk et al. 2012). A
paper-based colorimetric biosensing device was fabricated
for the detection of PSA, hydrogen peroxide and glucose
with detection range of 0.1-10 ng/mL (Zhou et al. 2014).
A paper-based immunochromatographic biosensor (POC)
for PSA detection was fabricated using quantum dots with
LOD of 0.02 ng/mL (Liu et al. 2007).
A low-cost µPADS can be fabricated using paper-based
microfluidic technique and using wax screen printing to
create hydrophilic/hydrophobic channels on the substrate.
This technique can be used for both colorimetric as well as
electrochemical detection (Dungchai et al. 2011). The vis-
ible color changes were interpreted with imaging software
for estimating the analyte concentration.
4.3 Field effect transistor (FET) based biosensor
The field-effect transistor-based biosensor (BioFET) uses
a biological recognition element attached with a FET
(Maddalena et al. 2010; Lee et al. 2014), where the charge
or the potential effect, is used to detect the analyte. BioFETs
are generally fabricated from an ISFET (ion-sensitive FET)
by customizing the gate or coupling it with different biore-
ceptors (Schoning and Poghossian 2002). A bio-recognition
layer is attached chemically or electrostatically on the trans-
ducer surface (Fig. 6). Carriers of charge travel from the
source (S) to the drain electrode (D) when bias voltage is
applied and the flow of charge-carriers is restricted by a
third electrode, gate (G). A BioFET is switched on or off by
applying an electrical potential at the gate. The biochemical
binding on the surface of the transducer is then converted to
a measurable electronic signal.
PSA was detected with a LOD of 1 fg/mL using a molyb-
denum disulfide ­(MoS2) FET biosensor. DNA tetrahedron
and biotin-streptavidin were conjugated to the FET which
enhanced the antigen-antibody binding (Zhang et al. 2021).
A graphene FET (POC) was fabricated to detect PSA with
LOD of 1 pg/mL (Mandal et al. 2021). A silicon nanow-
ire FET was fabricated for instantaneous detection of PSA.
Gold nanoparticles were used for functionalization of the
nanowires which added a covalent attachment of antibod-
ies through their thiol groups, which resulted higher effi-
ciency of the transistor and LOD of 23 fg/mL (Presnova
et al. 2017). Rodriguez et al. (2019) used gold nanoparticles
to fabricate a porous silicon FET biosensor for PSA detec-
tion using conductance of the FET with LOD of 0.1 ng/mL.
Another single-walled CNT FET based biosensor was fabri-
cated for instantaneous and sensitive protein detection with
LOD of 84 pM (Chen et al. 2016). The PSA was detected
using indium oxide (In2O3) nanowires and SWCNT as a
FET biosensor and using anti-PSA antibody with LOD of 5
ng/mL (Lee et al. 2012).
4.4 Challenges and future prospects
The development of biosensors has progressed a lot since
its emergence in the medical field. But technology always
leaves behind some alternatives which need further research
13
 32   Page 8 of 12 Biomedical Microdevices (2022) 24:32

and improvement. The main challenges are recognizing

Fig. 6  Schematic diagram of a BioFET. Reproduced with permission
from Schoning and Poghossian (2002)
small molecules, achieving better sensitivity and selectivity
in detecting different analytes, cross-linking, and immobi-
lization of bioreceptors on the substrate. Diagnosis of PCs
requires the detection of multiple biomarkers at the same
time using an individual chip. In the near future, biomarkers
pattern software and microfluidics can be included to make
promising devices for application in this area (Tothill 2009).
Amplification of sensitivity of biosensors has been a major
issue. Several processes for enhancing the sensitivity have
been used. Nanorods with high aspect ratio are preferred
over the spherical nanoparticles to improve sensitivity
of these devices. The observation of protein and protein
interactions poses a greater challenge than that of nucleic
acids as new amplification technologies are not available.
Complex association of the proteins and their stronger non-
specific binding to solid supports also adds to this scenario.
Hence, the nanoparticles which contain mixed monolayers
are expected to fully promote the potentiality of protein-
nanoparticle hybrids (Wang 2005).

Table 1  Types of biosensors used for detection of PC

Sl. No. Type of biosensors Biomarkers Limit of Detection (LOD) Reference

1. Electrochemical VEGF and PSA 0.05-100 ng/mL (for VEGF) and 1-100 ng/mL (for PSA) (Pan et al. 2017)
2. Electrochemical PSA 0.02 ng/mL (Lin et al. 2008)
3. Electrochemical miRNA-141 N/A (Tran et al. 2013)
4. Electrochemical Free PSA 0.1 ng/mL (Sarkar et al. 2008)
5. Electrochemical Total PSA N/A (Sarkar et.al. 2002)
6. Electrochemical PSA 10 ng/mL (Jolly et al. 2017)
7. Electrochemical PSA 15 fg/mL (Sharafeldin et al. 2017)
8. Electrochemical PSA 0.02 fg/mL (Zhu et al. 2016)
10. Optical PSA 10 fg/mL (Jin et al. 2012)
11. Optical Total PSA 0.25 ng/mL (Kerman et al. 2007)
12. Optical PSA N/A (Jang et al. 2009)
13. Optical PSA 0.1 ng/mL (Kim et al. 2019)
14. Optical PSA 100 pg/mL (Esseghaier et al. 2014)
15. Optical PSA 500 pg/mL (Acimovic et al. 2014)
16. Optical CEA and PSA 0.3 ng/mL (for CEA) and 0.4 ng/mL (for PSA) (Chen et al. 2019)
17. Piezoelectric PSA and AFP 0.25 ng/mL (Su et al. 2017)
18. Piezoelectric PSA N/A (Lee et al. 2005)
19. Piezoelectric PSA N/A (Gopinath et al. 2015)
20. Paper based PCA3 3 fM (Fu et.al. 2019)
21. Paper based PSA 0.33 ng/mL (Li et al. 2014)
22. Paper based fPSA 0.01 ng/mL (Salminen et.al. 2019)
23. Paper based PSA 0.06 ng/mL (Zhang et al. 2018)
24. Paper based PSA,AFP and CEA 2.05 pg/mL (for PSA), 3.30 pg/mL (for AFP) and 4.92 pg/ (Fang et al. 2018)
mL (for CEA)
25. Paper based PSA 10 ng/mL (Zhou et al. 2014)
26. Paper based PSA 0.02 ng/mL (Liu et al. 2007)
27. FET PSA 1 pg/mL (Mandal et al. 2021)
28. FET PSA 23 fg/mL (Presnova et al. 2017)
29. FET PSA 0.1 ng/mL (Rodriguez et al. 2019)

13
Biomedical Microdevices (2022) 24:32 Page 9 of 12  32
Most of the sensors need calibration before every use and
incubation in buffer solutions. Some sensors can detect the
analyte only at a certain level of concentration. The stability
of the biosensor also adds to this factor. Biosensors depend
on the bioreceptors, and the long-term storage and usage
of bioreceptors is a big challenge as bioreceptors are sus-
ceptible to changes in temperature, pressure, and pH value.
Any alterations in the normal environment conditions might
result in a decrease of the sensing ability. Biosensor with a
higher stability range is much more preferred as the condi-
tions of the environment keep on changing over the period
of time. In the present scenario, the stability of the biosen-
sors in a changing environment is quite a big challenges.
It has also been reported that sometimes biosensors need
to detect multiple analytes for specificity. Some specific
cancerous cells might require more than one analyte for its
confirmation. Hence, to achieve the greater specificity of
the biosensor dual-sensing capacity needs to be developed
(Liu et al. 2017).
Biosensors are becoming indispensable in today's world
due to their enormous potential in both research and commer-
cial applications. Combination of microfluidic technology
and 3D printing helps in reduction in cost and detection of
multiple analytes. However, according to the World Health
Organization (WHO), we should have ASSURED (afforda-
ble, sensitive, specific, user-friendly, rapid and robust, equip-
ment free, and delivered to those in need) devices to cater to
the needs of the masses (Srinivasan and Tung 2015).
5 Conclusion
The present review deals with the different issues related
to biosensors applied for detection of PC. The conven-
tional screening methods like DRE, PSA tests, US imag-
ing, and MRI are either not efficient in detecting PCs or
are very expensive. The expensive diagnosis methods are
not affordable to the common masses. Hence, biosensors
with capability to detect multiple biomarkers for efficient
PC detection are need of the hour. Though there are many
hurdles in biosensor development, extensive research work
is going on to develop different futuristic POC biosensors
and notable progress has been achieved in recent years. Inte-
gration of microfluidics, 3D printing, and artificial intelli-
gence techniques will have a significant effect in engineering
ASSURED biosensors for early detection of PC (Table 1).
Abbreviations  PC: Prostate cancer; DRE: Digital rectal examination;
TRUS: Transrectal Ultrasound; GSU: Gray-scale ultrasonography; PET/
CT: Positron emission tomography/computer tomography scan; PDU: Power
doppler ultrasonography; 3D-CE-PDU:  Three-dimensional contrast-
enhanced power doppler ultrasonography; TMRI: Transrectal magnetic
resonance imaging; PSA: Prostate-specific antigen; ELISA: Enzyme-
linked immunosorbent assay; SPE: Screen-printed electrodes; LOD: Limit
of detection; VEGF: Vascular endothelial growth factor; MEMS: Micro-
electromechanical systems; SPR: Surface plasmon resonance; QD: Quan-
tum dot; LSPR: Localized surface plasmon resonance; QCM: Quartz crys-
tal microbalance; PZT: Lead titanate zirconate; LFA: Lateral flow assay;
µPAD: Microfluidic paper-based analytical devices; POC: Point- of- care
Acknowledgment  We sincerely acknowledge the generous fund-
ing received from the Department of Biotechnology, India (No. BT/
PR24652/NER/95/795/2017; Dated: 06/03/2019), sanctioned to Dr.
Manashjit Gogoi for carrying out this piece of work. Also SERB, Govt
of India is acknowledged for SERB project (No. EMR/2016/002634)
sanctioned to Dr. Mrityunjoy Mahato.
Declarations 
Conflict of Interest  The authors declare that they have no conflict of
interest.
References
S.S. Acimovic, M.A. Ortega, V. Sanz, J. Berthelot, J.L. Garcia-
Cordero, J. Renger, S.J. Maerkl, M.P. Kreuzer, R. Quidant,
LSPR chip for parallel, rapid, and sensitive detection of cancer
markers in serum. Nano Lett. 14(5), 263–264 (2014). https://​
doi.​org/​10.​1021/​nl500​574n
V. Amendola, R. Pilot, M. Frasconi, O.M. Marago, M.A. Iatì, Sur-
face plasmon resonance in gold nanoparticles: a review. J. Phys.
Cond. Matt. 29(20), (2017)
M.A. Arugula, A. Simonian, Novel trends in affinity biosensors: cur-
rent challenges and perspectives. Meas. Sci. Technol. 25(3),
(2014)
E.H. Ayat, M.M. Darabi, N. Mohammadian, M. Parizadi, T. Kianoush,
K.M. Khabazand F. Kamalian, Ratios of Free to Total Prostate-
Specific Antigen and Total Prostate-Specific Antigen to Protein
Concentrations in Saliva and Serum of Healthy Men. Urol. J. 4(4),
238–241 (2007). https://​doi.​org/​10.​1016/j.​urolo​gy.​2009.​07.​55
M. Barceló, M. Castells, L. Bassas, F. Viguésand S. Larriba, Semen
miRNAs contained in exosomes as non-invasive biomarkers for
prostate cancer diagnosis. Sci. Reps. 9(1), 1–16 (2019). https://​
doi.​org/​10.​1038/​s41598-​019-​50172-6
C. Becker, T. Piironen, K. Pettersson, T.H.O.M.A.S. BJöRK, K.J.
Wojno, J.E. Oesterling and H. Lilja, Discrimination of men with
prostate cancer from those with benign disease by measurements
of human glandular kallikrein 2 (HK2) in serum. J. Urol. 163(1),
311–316 (2000)
Y. Chang, M. Wang, L. Wang, N. Xia, Recent progress in electrochemi-
cal biosensors for detection of prostate-specific antigen. Int. J.
Electrochem. Sci. 13(5), 4071–4084 (2018). https://​doi.​org/​10.​
20964/​2018.​05.​24
Y. Chen, X. Guo, W. Liu, L. Zhang, L, Paper based fluorometric
immune device with quantum-dot labeled antibodies for simul-
taneous detection of carcinoembryonic antigen and prostate
specific antigen. Microchim. Acta. 186(2), 1–9 (2019). https://​
doi.​org/​10.​1007/​s00604-​019-​3232-0
C. Chen, J. Wang, Optical biosensors: an exhaustive and comprehen-
sive review. Analyst 145(5), 1605–1628 (2020). https://​doi.​org/​
10.​1039/​c9an0​1998g
H. Chen, J. Huang, D.W.H. Fam, A.I.Y. Tok, Horizontally aligned carbon
nanotube based biosensors for protein detection. Bioengineering
3(4), 23 (2016). https://​doi.​org/​10.​3390/​bioen​ginee​ring3​040023
L.C. Clark Jr, C. Lyons. Electrode systems for continuous monitoring
in cardiovascular surgery. Annals of the New York Academy of
Sci. 102(1), 29–45 (1962). https://​doi.​org/​10.​1111/​nyas.​1962.​
102.​issue-1
13
 32   Page 10 of 12
P. Damborský, J. Šviteland J. Katrlík. Optical biosensors. Essays
in Biochem. 60(1), 91–100 (2016). https://​d oi.​o rg/​1 0.​1 042/​
ebc20​150010
W. Dungchai, O. Chailapakul, C.S. Henry, A low-cost, simple, and
rapid fabrication method for paper-based microfluidics using
wax screen-printing. Analyst 136(1), 77–82 (2011). https://​doi.​
org/​10.​1039/​c0an0​0406e
G. Ertürk, H.Özen, M.A. Tümer, B. Mattiassonand A. Denizli, Micro-
contact imprinting based surface plasmon resonance (SPR)
biosensor for real-time and ultrasensitive detection of pros-
tate specific antigen (PSA) from clinical samples.&nbsp;Sens.
Actuators B&nbsp;Chem. 224, 823–832 (2016). https://​doi.​org/​
10.​1016/j.​snb.​2015.​10.​093
T. Endo, S. Yamamura, N.Nagatani, Y. Morita, Y. Takamura, E.
Tamiya, Localized surface plasmon resonance based optical
biosensor using surface modified nanoparticle layer for label-
free monitoring of antigen–antibody reaction. Sci. Technol.
Adv. Maters. 6(5), 491(2005). https://​doi.​org/​10.​1016/j.​stam.​
2005.​03.​019
C. Esseghaier, G.A. Suaifan, A. Ng, M. Zourob, One-step assay for
optical prostate specific antigen detection using magnetically
engineered responsive thin film. J. Biomed. Nanotechnol.
10(6), 1123–1129 (2014). https://​doi.​org/​10.​1166/​jbn.​2014.​
1803
H. Farahani, M. Alaee, J. Amri, M.R. Baghiniaand M. Rafiee, Serum
and Saliva Concentrations of Biochemical Parameters in Men
with Prostate Cancer and Benign Prostate Hyperplasia. Lab.
Med. 51(3), 243–251 (2020). https://​doi.​org/​10.​1093/​labmed/​
lmz053
C.C. Fang, C.C. Chou, Y.Q. Yang, T. Wei-Kai, Y.T., Wang. and Y.H.
Chan, Multiplexed detection of tumor markers with multicolor
polymer dot-based immunochromatography test strip. Anal.
Chem. 90(3), 2134–2140 (2018). https://​doi.​org/​10.​1021/​acs.​
analc​hem.​7b044​11
Z. Feng, S. Zhi, L. Guo, Y. Zhou, C. Lei, An integrated magnetic
microfluidic chip for rapid immunodetection of the prostate
specific antigen using immunomagnetic beads. Microchim.
Acta 186(4), 1–14 (2019)
M. Ferro, C. Buonerba, D. Terracciano, G. Lucarelli, V. Cosimato,
D. Bottero, V.M. Deliu, P. Ditonno, S. Perdonà, R. Autorino, I.
Coman, Biomarkers in localized prostate cancer. Future Oncol.
12(3), 399–411 (2016)
X. Fu, J. Wen, J. Li, H. Lin, Y. Liu, X. Zhuang, C. Tian, L. Chen, Highly
sensitive detection of prostate cancer specific PCA3 mimic DNA
using SERS-based competitive lateral flow assay. Nanoscale
11(33), 15530–15536 (2019). https://​doi.​org/​10.​1039/​c9nr0​4864b
P. Gopinath, V. Anitha, S.A. Mastani, Microcantilever based biosen-
sor for disease detection applications. J. Med. Bioeng. 4, 34
(2015). https://​doi.​org/​10.​12720/​jomb.4.​4.​307-​311
T. Gutschner, S. Diederichs, The hallmarks of cancer: a long non-
coding RNA point of view. RNA Biol. 9(6), 703–719 (2012)
R. Gupta, S. Swaminathan, Modeling and simulation of piezoelectric
based micro cantilever systems for Prostate Specific Antigen,
International Symposium on Next-Generation Electronics
(ISNE) 1–3 (2015). IEEE. https://​doi.​org/​10.​1109/​isne.​2015.​
71319​50
S. Hachuda, T. Watanabe, D. Takahashi, T. Baba, 2015, May. Sensi-
tive and selective detection of prostate specific antigen beyond
ELISA using photonic crystal nanolaser. In&nbsp;2015 Con-
ference on Lasers and Electro-Optics (CLEO) (pp. 1–2). IEEE.
https://​doi.​org/​10.​1364/​cleo_​at.​2015.​am1j.3
E.J. Halpern, Contrast-enhanced ultrasound imaging of prostate can-
cer. Reviews in urology 8(Suppl 1), S29 (2006)
K. Hariharan, V. Padmanabha, Demography and disease characteris-
tics of prostate cancer in India. Indian J. Uro 32(2), 103 (2016).
https://​doi.​org/​10.​4103/​0970-​1591.​174774
13
Biomedical Microdevices (2022) 24:32
H. Härmä, T. Soukka, T. Lövgren, Europium nanoparticles and time-
resolved fluorescence for ultrasensitive detection of prostate-
specific antigen. Clin. Chem. 47(3), 561–568 (2001). https://​
doi.​org/​10.​1093/​clinc​hem/​47.3.​561
J. Homola, Surface plasmon resonance sensors for detection of chemi-
cal and biological species. Chem. Rev. 108(2), 462–493 (2008).
https://​doi.​org/​10.​1021/​cr068​107d
J. Homola, S.S. Yee, G. Gauglitz, Surface plasmon resonance sensors.
Sens. Actuators B 54(1–2), 3–15 (1999). https://d​ oi.o​ rg/1​ 0.1​ 016/​
s0925-​4005(98)​00321-9
X.D. Hoa, A.G. Kirk, M. Tabrizian, Towards integrated and sensi-
tive surface plasmon resonance biosensors: a review of recent
progress.&nbsp;Biosens. Bioelectron. 23(2), 151–160 (2007).
https://​doi.​org/​10.​1016/j.​bios.​2007.​07.​001
J. Hu, S. Wang, L. Wang, F. Li, B. Pingguan-Murphy, T.J. Lu, F. Xu,
Advances in paper-based point-of-care diagnostics. Biosens. Bio-
electron. 54, 585–597 (2014)
J. Hu, J.R. Choi, S. Wang, Y. Gong, S. Feng, B. Pingguan-Murphy,
T.JLu.F. Xu, Multiple test zones for improved detection perfor-
mance in lateral flow assays. Sensors Actuators B Chem. 243,
484–488 (2017)
H.S. Jang, K.N. Park, C.D. Kang, J.P. Kim, S.J. Sim, K.S. Lee, Opti-
cal fiber SPR biosensor with sandwich assay for the detection
of prostate specific antigen. Opt. Comm. 282(14), 2827–2830
(2009). https://​doi.​org/​10.​1016/j.​optcom.​2009.​03.​078
L.H. Jin, S.M. Li, Y.H. Cho, Enhanced detection sensitivity of pegylated
CdSe/ZnS quantum dots-based prostate cancer biomarkers by sur-
face plasmon-coupled emission. Biosens. Bioelectron. 33(1), 284–287
(2012). https://​doi.​org/​10.​1016/j.​bios.​2011.​12.​043
P. Jolly, P. Zhurauski, J.L. Hammond, A. Miodek, S. Liébana, T. Ber-
tok, J. Tkáč, P. Estrela, Self-assembled gold nanoparticles for
impedimetric and amperometric detection of a prostate can-
cer biomarker. Sensors and Actuators B: Chem. 251, 637–643
(2017). https://​doi.​org/​10.​1016/j.​snb.​2017.​05.​040
B. Jurado-Sánchez, Nanoscale biosensors based on self-propelled
objects. Biosensors 8(3), 59 (2018). https://​doi.​org/​10.​3390/​
bios8​030059
J.T. Kearns, D.W. Lin, Improving the specificity of PSA screening with
serum and urine markers. Current urology reports 19(10), 1–4
(2018). https://​doi.​org/​10.​1007/​s11934-​018-​0828-6
Key Statistics for Prostate Cancer, American cancer society. https://​
www.c​ ancer.o​ rg/c​ ancer/p​ rosta​ te-c​ ancer/a​ bout/k​ ey-s​ tatis​ tics.h​ tml.
Viewed on 30 Sept 2021
K. Kerman, T. Endo, M. Tsukamoto, M. Chikae, Y. Takamura, E.
Tamiya, Quantum dot-based immunosensor for the detection of
prostate-specific antigen using fluorescence microscopy. Talanta
71(4), 1494–1499 (2007). https://d​ oi.o​ rg/1​ 0.1​ 016/j.t​ alant​ a.2​ 006.​
07.​027
M.S. Khan, K. Dighe, Z. Wang, I. Srivastava, E. Daza, A.S. Schwartz-
Dual, J. Ghannam, S.K. Misra, D. Pan, Detection of prostate spe-
cific antigen (PSA) in human saliva using an ultra-sensitive nano-
composite of graphene nanoplatelets with diblock-co-polymers
and Au electrodes. Analyst 143(5), 1094–1103 (2018). https://​
doi.​org/​10.​1039/​c7an0​1932g
H.M. Kim, M. Uh, D.H. Jeong, H.Y. Lee, J.H. Park, S.K. Lee, Local-
ized surface plasmon resonance biosensor using nanopatterned
gold particles on the surface of an optical fiber. Sens. Actuators
B: Chem. 280, 183–191 (2019)
A.P. Kirkham, M. Emberton, C. Allen, How good is MRI at detecting
and characterising cancer within the prostate? European Urol.
50(6), 1163–1175 (2006). https://​doi.o​ rg/​10.​1016/j.​eururo.​2006.​
06.​025
G.G. Klee, M.K. Goodmanson, S.J. Jacobsen, C.Y. Young, J.A. Finlay,
H.G. Rittenhouse, R.L. Wolfert, D.J. Tindall, Highly sensitive
automated chemiluminometric assay for measuring free human
glandular kallikrein-2. Clin. Chem. 45(6), 800–806 (1999)
Biomedical Microdevices (2022) 24:32 Page 11 of 12  32
J. Kwak, S.S. Lee, Highly sensitive piezoelectric immunosensors
employing signal amplification with gold nanoparticles. Nano-
technology 30(44), 445502 (2019)
S.H. Lee, J.H., Sung and T.H. Park, Nanomaterial-based biosen-
sor as an emerging tool for biomedical applications. Annals
Biomed. Eng. 40(6), 1384–1397 (2012). https://​d oi.​o rg/​1 0.​
1007/​s10439-​011-​0457-4
J.H. Lee, K.S. Hwang, J. Park, K.H. Yoon, D.S. Yoon, T.S. Kim,
Immunoassay of prostate-specific antigen (PSA) using resonant
frequency shift of piezoelectric nanomechanical microcantile-
ver. Biosens. Bioelectron. 20(10), 2157–2162 (2005)
L.G. Lee, E.S. Nordman, M.D. Johnson, M.F. Oldham, A low-cost,
high-performance system for fluorescence lateral flow assays.
Biosensors 3(4), 360–373 (2013). https://​doi.​org/​10.​3390/​bios3​
040360
J. Lee, P. Dak, Y. Lee, H. Park, W. Choi, M.A. Alam, S. Kim, Two-
dimensional layered MoS2 biosensors enable highly sensitive
detection of biomolecules. Sci. Reps. 4(1), 1–7 (2014). https://​
doi.​org/​10.​1038/​srep0​7352
X. Li, W. Li, Q. Yang, X. Gong, W. Guo, C. Dong, J. Liu, L. Xuan,
J. Chang, Rapid and quantitative detection of prostate specific
antigen with a quantum dot nanobeads-based immunochroma-
tography test strip. ACS Appl. Mater. Interf. 6(9), 6406–6414
(2014). https://​doi.​org/​10.​1021/​am501​2782
Y.Y. Lin, J. Wang, G. Liu, H. Wu, C.M. Wai, Y. Lin, A nanoparticle
label/immunochromatographic electrochemical biosensor for
rapid and sensitive detection of prostate-specific antigen. Bios-
ens. Bioelectron. 23(11), 1659–1665 (2008). https://​doi.​org/​10.​
1016/j.​bios.​2008.​01.​037
G. Liu, Y.Y. Lin, J. Wang, H. Wu, C.M. Wai, Y. Lin, Disposable elec-
trochemical immunosensor diagnosis device based on nano-
particle probe and immunochromatographic strip. Anal. Chem.
79(20), 7644–7653 (2007)
X. Liu, M. Mwangi, X. Li, M. O'Brien, G.M. Whitesides, Paper based
piezoresistive MEMS sensors. Lab on a Chip 11(13), 2189–2196
(2011). https://​doi.​org/​10.​1039/​c1lc2​0161a
T. Liu, N. Li, J.X. Dong, Y. Zhang, Y.Z. Fan, S.M. Lin, H.Q. Luo,
N.B. Li, A colorimetric and fluorometric dual-signal sensor for
arginine detection by inhibiting the growth of gold nanoparti-
cles/carbon quantum dots composite. Biosens. Bioelectron. 87,
772–778 (2017). https://​doi.​org/​10.​1016/j.​bios.​2016.​08.​098
R. Lin, A. Skandarajah, R.E. Gerver, H.D. Neira, D.A. Fletcher, A.E.
Herr, A lateral electrophoretic flow diagnostic assay. Lab on a
Chip 15(6), 1488–1496 (2015). https://​doi.​org/​10.​1039/​c4lc0​1370k
A.A. Luderer, Y.T. Chen, T.F. Soriano, W.J. Kramp, G. Carlson, C. Cuny,
T. Sharp, W. Smith, J. Petteway, M.K. Brawer, R. Thiel, Measure-
ment of the proportion of free to total prostate-specific antigen
improves diagnostic performance of prostate-specific antigen in
the diagnostic gray zone of total prostate-specific antigen. Urology
46(2), 187–194 (1995)
F. Maddalena, M.J. Kuiper, B. Poolman, F. Brouwer, J.C. Hummelen,
D.M. de Leeuw, B. De Boer, P.W. Blom, P, Organic field-effect
transistor-based biosensors functionalized with protein receptors.
J. Appl. Phys. 108(12), (2010)
N. Mandal, V. Pakira, N. Samanta, N. Das, S. Chakraborty, B. Pra-
manick, C. RoyChaudhuri, PSA detection using label free gra-
phene FET with coplanar electrodes based microfluidic point
of care diagnostic device. Talanta 222, 121581 (2021). https://​
doi.​org/​10.​1016/j.​talan​ta.​2020.​121581
G. Marrazza, Piezoelectric biosensors for organophosphate and carba-
mate pesticides: a review. Biosensors 4(3), 301–317 (2014). https://​
doi.​org/​10.​3390/​bios4​030301
Z. Mao, A. Ji, K. Yang, W. He, Y. Hu, Q. Zhang, D. Zhang, L. Xie,
Diagnostic performance of PCA3 and hK2 in combination
with serum PSA for prostate cancer. Medicine 97(42), (2018).
https://​doi.​org/​10.​1097/​md.​00000​00000​012806
B.R. Matlaga, L.A. Eskew, D.L. McCULLOUGH, Prostate biopsy:
indications and technique. J. Urol. 169(1), 12–19 (2003).
https://​doi.​org/​10.​1097/​00005​392-​20030​1000-​00004
E.W. Nery, L.T. Kubota, Sensing approaches on paper-based devices:
a review. Anal. Bioanal. Chem. 405(24), 7573–7595 (2013)
L.H. Pan, S.H. Kuo, T.Y. Lin, C.W. Lin, P.Y. Fang, H.W. Yang, An
electrochemical biosensor to simultaneously detect VEGF and
PSA for early prostate cancer diagnosis based on graphene
oxide/ssDNA/PLLA nanoparticles. Biosens. Bioelectron.
89(1), 598–605 (2017). https://​doi.​org/​10.​1016/j.​bios.​2016.​
01.​077
W. Pang, H. Zhao, E.S. Kim, H. Zhang, H. Yu, X. Hu, Piezoelectric
microelectromechanical resonant sensors for chemical and bio-
logical detection. Lab on a Chip 12(1), 29–44 (2012). https://​
doi.​org/​10.​1039/​c1lc2​0492k
E. Petryayeva, U.J. Krull, Localized surface plasmon resonance:
Nanostructures, bioassays and biosensing—A review. Anal.
Chim. Acta 706(1), 8–24 (2011). https://​doi.​org/​10.​1016/j.​aca.​
2011.​08.​020
G.A. Posthuma-Trumpie, J. Korf, A. van Amerongen, Lateral flow
(immuno) assay: its strengths, weaknesses, opportunities and
threats. A literature survey, Anal. Bioanal. Chem. 393(2),
569–582 (2009). https://​doi.​org/​10.​1007/​s00216-​008-​2287-2
G. Presnova, D. Presnov, V. Krupenin, V. Grigorenko, A. Trifonov,
I. Andreeva, O. Ignatenko, A. Egorov, M. Rubtsova, Biosensor
based on a silicon nanowire field-effect transistor functionalized
by gold nanoparticles for the highly sensitive determination of
prostate specific antigen. Biosens. Bioelectron. 88, 283–289
(2017). https://​doi.​org/​10.​1016/j.​bios.​2016.​08.​054
P. Puech, O. Rouvière, R. Renard-Penna, A. Villers, P. Devos, M.
Colombel, M.O. Bitker, X. Leroy, F. Mège-Lechevallier, E.
Comperatand A. Ouzzane, Prostate cancer diagnosis: mul-
tiparametric MR-targeted biopsy with cognitive and transrectal
US–MR fusion guidance versus systematic biopsy—prospective
multicenter study. Radiology 268(2), 461–469 (2013). https://​
doi.​org/​10.​1148/​radiol.​13121​501
J.J. Ramsden, Optical biosensors. J. Mol. Recogn. 10(3), 109–120
(1997). https://​doi.​org/​10.​1002/​(sici)​1099-​1352(199705/​06)​10:​
3<​109::​aid-​jmr36​1>3.​0.​co;2-d
K. Ratajczak, M. Stobiecka, High-performance modified cellulose
paper-based biosensors for medical diagnostics and early
cancer screening: A concise review. Carbohydr. Polym. 229,
(2020)
A.R. Rezk, A. Qi, J.R. Friend, W.H. Li, L.Y. Yeo, Uniform mixing in
paper-based microfluidic systems using surface acoustic waves.
Lab on a Chip 12(4), 773–779 (2012). https://​doi.​org/​10.​1039/​
c2lc2​1065g
C. Rodriguez, P. Dietrich, V. Torres-Costa, V. Cebrián, C. Gómez-
Abad, A. Díaz, O. Ahumada, M.M. Silván, Near ambient
pressure X-ray photoelectron spectroscopy monitoring of the
surface immobilization cascade on a porous silicon-gold nano-
particle FET biosensor. Applied Surface Science 492, 362–368
(2019). https://​doi.​org/​10.​1016/j.​apsusc.​2019.​06.​056
T. Salminen, E. Juntunen, S.M. Talha, K. Pettersson, High-sensitivity
lateral flow immunoassay with a fluorescent lanthanide nano-
particle label. J. Imm. Methods 465, 39–44 (2019). https://​doi.​
org/​10.​1016/j.​jim.​2018.​12.​001
A.K. Sana, Y. Amemiya, T. Ikeda, A. Kuroda, S. Yokoyama, Detection
of prostate specific antigen using silicon photonic crystal nano-
cavity resonator. In&nbsp;Quantum Sensing and Nano Electron-
ics and Photonics XIV (Vol. 10111, p. 1011138). Int. Soc. Opt.
Photon. (2017). https://​doi.​org/​10.​1117/​12.​22516​04
M. Sanders, Y. Lin, J. Wei, T. Bono, R.G. Lindquist, An enhanced
LSPR fiber-optic nanoprobe for ultrasensitive detection of
protein biomarkers. Biosens. Bioelectron. 61, 95–101 (2014).
https://​doi.​org/​10.​1016/j.​bios.​2014.​05.​009
13
 32   Page 12 of 12
K.E. Sapsford, T. Pons, I.L. Medintzand, H. Mattoussi, Biosensing
with luminescent semiconductor quantum dots. Sensors 6(8),
925–953 (2006)
P. Sarkar, D. Ghosh, D. Bhattacharyay, S.E. Setford, A.E.E. Turner, Elec-
trochemical immunoassay for Free prostate specific antigen (f‐PSA)
using magnetic beads. Electroanalysis: An Int. J. Devoted to Fun-
damental and Practical Aspects of Electroanal. 20(13), 1414–1420
(2008). https://​doi.​org/​10.​1002/​elan.​20080​4194
P. Sarkar, P.S. Pal, D. Ghosh, S.J. Setford, I.E. Tothill, Amperometric
biosensors for detection of the prostate cancer marker (PSA).
Int. J. Pharmaceutics 238(1–2), 1–9 (2002). https://​doi.​org/​10.​
1016/​s0378-​5173(02)​00015-7
D.T. Schmid, H. John, R. Zweifel, T. Cservenyak, G. Westera, G.W.
Goerres, G.K. von Schulthess, T.F. Hany, Fluorocholine PET/
CT in patients with prostate cancer: initial experience. Radiol-
ogy 235(2), 623–628 (2005)
M.J. Schöning, A. Poghossian, Recent advances in biologically sen-
sitive field-effect transistors (BioFETs). Analyst 127(9), 1137–
1151 (2002)
F.H. Schröder, A.B. Kruger, J. Rietbergen, R. Kranse, P.V.D. Maas, P.
Beemsterboer, R. Hoedemaeker, Evaluation of the digital rectal
examination as a screening test for prostate cancer. J. Nat. Cancer
Ins. 90(23), 1817–1823 (1998). https://​doi.​org/​10.​1093/​jnci/​90.​
23.​1817
Y. Seto, T. Iba, K. Abe, Development of ultra-high sensitivity biolumi-
nescent enzyme immunoassay for prostate-specific antigen (PSA)
using firefly luciferase. Luminescence 16(4), 285–290 (2001).
https://​doi.​org/​10.​1002/​bio.​654
M. Sharafeldin, G.W. Bishop, S. Bhakta, A. El-Sawy, S.L. Suib, J.F.
Rusling, Fe3O4 nanoparticles on graphene oxide sheets for
isolation and ultrasensitive amperometric detection of cancer
biomarker proteins.&nbsp;Biosens. Bioelectron. 91, 359–366
(2017). https://​doi.​org/​10.​1016/j.​bios.​2016.​12.​052
M.A. Shergujri, R. Jaman, A.J. Baruah, M. Mahato, D. Pyngrope, L.R.
Singh, M. Gogoi, Based Sensors for Biomedical Applications. In
Biomedical Engineering and its Applications in Healthcare (pp.
355-376). Springer, Singapore (2019)
R.L. Siegel, K.D. Miller, A. Jemal, Cancer statistics. CA: A Cancer
J. Clin. 69(1), 7–34 (2019). https://​doi.​org/​10.​3322/​caac.​21551
J. Shen, L. Dudik, C.C. Liu, An iridium nanoparticles dispersed carbon
based thick film electrochemical biosensor and its application for
a single use, disposable glucose biosensor. Sensors and Actuators
B: Chem. 125(1), 106–113 (2007). https://​doi.​org/​10.​1016/j.​snb.​
2007.​01.​043
P. Skládal, Piezoelectric biosensors. TrAC Trends in Anal. Chem. 79,
127–133 (2016). https://​doi.​org/​10.​1016/j.​trac.​2015.​12.​009
B. Srinivasan, S. Tung, Development and applications of portable bio-
sensors. J. Lab. Autom. 20(4), 365–389 (2015)
U.H. Stenman, J. Leinonen, W.M. Zhangand, P. Finne, Prostate-specific
antigen. In Seminars in cancer biology, Academic Press 9(2),
83–93 (1999). https://​doi.​org/​10.​1006/​scbi.​1998.​0086
L.I. Stowell, L.E. Sharman, K. Hamel, An enzyme-linked immunosorb-
ent assay (ELISA) for prostate-specific antigen. Forensic Sci. Int.
50(1), 125–138 (1991). https://​doi.​org/​10.​1016/​0379-​0738(91)​
90141-5
L. Su, C.C. Fong, P.Y. Cheung, M. Yang, Development of novel piezo-
electric biosensor using pzt ceramic resonator for detection of
cancer markers. In Biosensors and biodetection (pp. 277–291).
Humana Press, New York, NY (2017)
L. Su, L. Zou, C.C. Fong, W.L. Wong, F. Wei, K.Y. Wong, R.S. Wu, M.
Yang, Detection of cancer biomarkers by piezoelectric biosensor
13
Biomedical Microdevices (2022) 24:32
using PZT ceramic resonator as the transducer. Biosens. Bioel-
ectron. 46, 155–161 (2013). https://​doi.​org/​10.​1016/j.​bios.​2013.​
01.​074
I.E. Tothill, February. Biosensors for cancer markers diagnosis. In
Seminars in cell & developmental biology&nbsp;(Vol. 20, No.
1, pp. 55–62). Academic Press (2009). https://​doi.​org/​10.​1016/j.​
semcdb.​2009.​01.​015
H.V. Tran, B. Piro, S. Reisberg, L.D. Tran, H.T. Duc, M.C. Pham,
Label-free and reagentless electrochemical detection of micro-
RNAs using a conducting polymer nanostructured by carbon
nanotubes: Application to prostate cancer biomarker miR-141.
Biosens. Bioelectron. 49(15), 164–169 (2013). https://​doi.​org/​
10.​1016/j.​bios.​2013.​05.​007
D. Unal, J.P.M. Sedelaar, R.G. Aarnink, G.J.L.H. Van Leenders, H.
Wijkstra, F.M.J. Debruyne, J.J.M.C.H. De La Rosette, Three‐
dimensional contrast‐enhanced power Doppler ultrasonography
and conventional examination methods: the value of diagnostic
predictors of prostate cancer. BJU International 86(1), 58–64
(2000). https://​doi.​org/​10.​1046/j.​1464-​410x.​2000.​00719.x
A.E. Urusov, A.V. Zherdev, B.B. Dzantiev, Towards lateral flow quantitative
assays: detection approaches. Biosensors 9(3), 89 (2019)
S.K. Vashist, A review of microcantilevers for sensing applications. J.
Nanotechnol. 3, 1–18 (2007)
J. Wang, Nanomaterial-based electrochemical biosensors. Analyst
130(4), 421–426 (2005). https://​doi.​org/​10.​1039/​b4142​48a
K.A. Willets, R.P. Van Duyne, Localized surface plasmon resonance
spectroscopy and sensing. Annu. Rev. Phys. Chem. 58, 267–297
(2007). https://​doi.​org/​10.​1146/​annur​ev.​physc​hem.​58.​032806.​
104607
J. Yao, Y. Wang, Y. Dai, C.C. Liu, Bioconjugated, Single-Use Bio-
sensor for the Detection of Biomarkers of Prostate Cancer,
ACS. Omega 3(6), 6411–6418 (2018). https://​doi.​org/​10.​1021/​
acsom​ega.​8b006​34
B. Zhang, W. Gao, J. Piao, Y. Xiao, B. Wang, W. Peng, X. Gong, Z. Wang,
H. Yang, J. Chang, Effective bioactivity retention of low-concentration
antibodies on HFBI-modified fluorescence ICTS for sensitive and rapid
detection of PSA. ACS Appl. Mater. Interf. 10(17), 14549–14558
(2018). https://​doi.​org/​10.​1021/​acsami.​8b029​45
Y. Zhang, D. Feng, Y. Xu, Z. Yin, W. Dou, U.E. Habiba, C. Pan, Z.
Zhang, H. Mou, H. Deng, X. Mi, DNA-based functionalization
of two-dimensional MoS2 FET biosensor for ultrasensitive detec-
tion of PSA. Appl. Surf. Sci. 548, (2021)
M. Zhou, M. Yang, F. Zhou, Paper based colorimetric biosensing plat-
form utilizing cross-linked siloxane as probe. Biosens. Bioelec-
tron. 55, 39–43 (2014). https://​doi.​org/​10.​1016/j.​bios.​2013.​11.​
065
Y. Zhu, H. Wang, L. Wang, J. Zhu, W. Jiang, Cascade signal amplifica-
tion based on copper nanoparticle-reported rolling circle amplifi-
cation for ultrasensitive electrochemical detection of the prostate
cancer biomarker. ACS Appl. Mater. Interf. 8(4), 2573–2581
(2016). https://​doi.​org/​10.​1021/​acsami.​5b102​85
Publisher's Note Springer Nature remains neutral with regard to
jurisdictional claims in published maps and institutional affiliations.
Springer Nature or its licensor holds exclusive rights to this article under
a publishing agreement with the author(s) or other rightsholder(s);
author self-archiving of the accepted manuscript version of this article
is solely governed by the terms of such publishing agreement and
applicable law.